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Eine Studie zur Bewertung mehrerer Therapien bei neu diagnostiziertem und rezidivierendem Glioblastom (GBM AGILE)

29. Oktober 2026 aktualisiert von: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: Eine internationale, nahtlose Phase-II/III-Response-Adaptive-Randomization-Platform-Studie zur Bewertung mehrerer Therapien bei neu diagnostiziertem und rezidivierendem GBM

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.

All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (*).

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. Its goals are to identify effective therapies for glioblastoma and match effective therapies with patient subtypes. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to Arms based on their performance. The primary endpoint is overall survival (OS).

GBM AGILE is designed to efficiently evaluate therapies. The trial will be conducted under a single Master Investigational New Drug Application/Clinical Trial Application and Master Protocol, allowing multiple drugs and drug combinations from different pharmaceutical companies to be evaluated simultaneously. The plan is to add experimental therapies as new information about promising new drugs are identified and remove therapies as they complete their evaluation.

Studientyp

Interventionell

Einschreibung (Geschätzt)

2250

Phase

  • Phase 2
  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

  • Australien
    • New South Wales
      • St Leonards, New South Wales, Australien, 2065
        • Rekrutierung
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Hauptermittler:
          • Helen Wheeler, MD
        • Kontakt:
      • Waratah, New South Wales, Australien, 2298
        • Aktiv, nicht rekrutierend
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Australien, 4029
        • Rekrutierung
        • Royal Brisbane and Women's Hospital
        • Hauptermittler:
          • Zarnie Lwin, MD
        • Kontakt:
    • South Australia
      • Bedford Park, South Australia, Australien, 5042
    • Victoria
      • Heidelberg, Victoria, Australien, 3084
      • Melbourne, Victoria, Australien
        • Rekrutierung
        • Peter MacCallum Cancer Centre
        • Hauptermittler:
          • Jim Whittle, MD
        • Kontakt:
        • Kontakt:
  • Deutschland
      • Cologne, Deutschland, 50937
        • Rekrutierung
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Kontakt:
        • Hauptermittler:
          • Norbert Galldiks, Prof.
      • Frankfurt, Deutschland, 60528
        • Rekrutierung
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Kontakt:
        • Hauptermittler:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Deutschland, 69120
        • Rekrutierung
        • Universitätsklinik Heidelberg
        • Hauptermittler:
          • Antje Wick, MD
        • Kontakt:
      • Mannheim, Deutschland, 68167
        • Rekrutierung
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Hauptermittler:
          • Michael Platten, MD
        • Kontakt:
      • Regensburg, Deutschland, 93053
        • Rekrutierung
        • Universitätsklinikum Regensburg
        • Hauptermittler:
          • Peter Hau, MD
        • Kontakt:
      • Tübingen, Deutschland, 72076
        • Rekrutierung
        • Universitätsklinikum Tübingen
        • Hauptermittler:
          • Ghazaleh Tabatabai, MD
        • Kontakt:
  • Frankreich
      • Bron, Frankreich, 69677
        • Rekrutierung
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Hauptermittler:
          • Francois Ducray, MD
        • Kontakt:
      • Marseille, Frankreich, 13005
        • Rekrutierung
        • Hopital de la Timone
        • Kontakt:
        • Hauptermittler:
          • Emelie Tabouret, MD
      • Paris, Frankreich, 75013
        • Rekrutierung
        • Hopital Piti-Salpetriere
        • Kontakt:
        • Hauptermittler:
          • Mehdi Touat, MD
  • Kanada
    • Ontario
      • Toronto, Ontario, Kanada, M4N 3M5
      • Toronto, Ontario, Kanada, M5G 2C1
        • Rekrutierung
        • Princess Margaret Cancer Centre
        • Hauptermittler:
          • Warren Mason, MD
        • Kontakt:
        • Kontakt:
    • Quebec
      • Montreal, Quebec, Kanada, H3A 2B4
        • Aktiv, nicht rekrutierend
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Kanada, J1H 5H3
        • Aktiv, nicht rekrutierend
        • Université de Sherbrooke
  • Schweiz
      • Zurich, Schweiz
        • Rekrutierung
        • University Hospital Zurich
        • Hauptermittler:
          • Michael Weller, MD
        • Kontakt:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Schweiz, 1011
        • Rekrutierung
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Hauptermittler:
          • Andreas Hottinger, MD
        • Kontakt:
  • Vereinigte Staaten
    • Alabama
      • Birmingham, Alabama, Vereinigte Staaten, 35249
        • Rekrutierung
        • University of Alabama at Birmingham
        • Hauptermittler:
          • Louis B Nabors, MD
        • Kontakt:
        • Kontakt:
    • California
      • La Jolla, California, Vereinigte Staaten, 92093
      • Los Angeles, California, Vereinigte Staaten, 90048
        • Aktiv, nicht rekrutierend
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, Vereinigte Staaten, 90095
        • Aktiv, nicht rekrutierend
        • University of California, Los Angeles
      • Orange, California, Vereinigte Staaten, 92868
        • Rekrutierung
        • St. Joseph Hospital
        • Hauptermittler:
          • Lars Anker, MD
        • Kontakt:
      • San Francisco, California, Vereinigte Staaten, 94143
        • Rekrutierung
        • University of California, San Francisco
        • Hauptermittler:
          • Nicholas Butowski, MD
        • Kontakt:
      • Stanford, California, Vereinigte Staaten, 94305
        • Abgeschlossen
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Vereinigte Staaten, 80045
        • Rekrutierung
        • University of Colorado Denver
        • Hauptermittler:
          • Denise Damek, MD
        • Kontakt:
    • Connecticut
      • New Haven, Connecticut, Vereinigte Staaten, 06511
        • Rekrutierung
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Hauptermittler:
          • Nicholas Blondin, MD
        • Kontakt:
    • Florida
      • Jacksonville, Florida, Vereinigte Staaten, 32224
        • Abgeschlossen
        • Mayo Clinic Cancer Center
      • Miami, Florida, Vereinigte Staaten, 33136
        • Rekrutierung
        • Sylvester Comprehensive Cancer Center*
        • Hauptermittler:
          • Macarena I De La Fuente, MD
        • Kontakt:
      • Tampa, Florida, Vereinigte Staaten, 33612
    • Georgia
      • Atlanta, Georgia, Vereinigte Staaten, 30309
        • Aktiv, nicht rekrutierend
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, Vereinigte Staaten, 30322
        • Aktiv, nicht rekrutierend
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, Vereinigte Staaten, 70112
        • Abgeschlossen
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, Vereinigte Staaten, 02114
        • Rekrutierung
        • Massachusetts General Hospital
        • Hauptermittler:
          • Patrick Wen, MD
        • Kontakt:
          • Patrick Wen, MD
          • Telefonnummer: 617-726-5130
          • E-Mail: pwen@mgb.org
      • Boston, Massachusetts, Vereinigte Staaten, 02115
    • Michigan
      • Detroit, Michigan, Vereinigte Staaten, 48202
        • Abgeschlossen
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, Vereinigte Staaten, 55407
        • Rekrutierung
        • Allina Health Systems/Abbott Northwestern Hospital
        • Hauptermittler:
          • Andrea Wasilewski, MD
        • Kontakt:
      • Rochester, Minnesota, Vereinigte Staaten, 55905
        • Abgeschlossen
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, Vereinigte Staaten, 39213
        • Abgeschlossen
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, Vereinigte Staaten, 63110
        • Abgeschlossen
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, Vereinigte Staaten, 10032
      • New York, New York, Vereinigte Staaten, 10016
        • Aktiv, nicht rekrutierend
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, Vereinigte Staaten, 10029
        • Aktiv, nicht rekrutierend
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Vereinigte Staaten, 10065
        • Rekrutierung
        • Memorial Sloan Kettering Cancer Center*
        • Hauptermittler:
          • Ingo Mellinghoff, MD
        • Kontakt:
        • Kontakt:
    • North Carolina
      • Durham, North Carolina, Vereinigte Staaten, 27710
        • Aktiv, nicht rekrutierend
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Vereinigte Staaten, 272157
        • Rekrutierung
        • Comprehensive Cancer Center of Wake Forest*
        • Hauptermittler:
          • Glenn Lesser, MD
        • Kontakt:
    • Ohio
      • Cleveland, Ohio, Vereinigte Staaten, 44195
        • Rekrutierung
        • Cleveland Clinic
        • Hauptermittler:
          • Mina Lobbous, MD
        • Kontakt:
        • Kontakt:
      • Cleveland, Ohio, Vereinigte Staaten, 44106
      • Columbus, Ohio, Vereinigte Staaten, 43210
        • Aktiv, nicht rekrutierend
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
        • Aktiv, nicht rekrutierend
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, Vereinigte Staaten, 15232
        • Aktiv, nicht rekrutierend
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, Vereinigte Staaten, 15212
        • Abgeschlossen
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, Vereinigte Staaten, 29425
        • Rekrutierung
        • Medical University of South Carolina - Hollings Cancer Center
        • Hauptermittler:
          • Scott Lindhorst, MD
        • Kontakt:
    • Texas
      • Austin, Texas, Vereinigte Staaten, 78705
        • Aktiv, nicht rekrutierend
        • Texas Oncology - Austin
      • Dallas, Texas, Vereinigte Staaten, 75390
        • Aktiv, nicht rekrutierend
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Vereinigte Staaten, 77030
        • Aktiv, nicht rekrutierend
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Vereinigte Staaten, 84112
        • Rekrutierung
        • University of Utah - Huntsman Cancer Institute
        • Hauptermittler:
          • Howard Colman, MD, PhD
        • Kontakt:
        • Kontakt:
    • Virginia
      • Charlottesville, Virginia, Vereinigte Staaten, 22908
        • Rekrutierung
        • University of Virginia Health
        • Kontakt:
        • Hauptermittler:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, Vereinigte Staaten, 98101
        • Aktiv, nicht rekrutierend
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Vereinigte Staaten, 53226
        • Rekrutierung
        • Froedtert Hospital/Medical College of Wisconsin
        • Hauptermittler:
          • Jennifer Connelly, MD
        • Kontakt:
        • Kontakt:

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Newly Diagnosed Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
  • Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from definitive surgery or biopsy.

Recurrent Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
  • Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
  • Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
  • Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Newly Diagnosed Exclusion Criteria:

  • Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Recurrent Exclusion Criteria:

  • Early disease progression prior to 3 months (12 weeks) from the completion of RT.
  • More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
  • Received any prior treatment with lomustine, agents part of any of the experimental arms, or bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
  • Any prior treatment with prolifeprospan 20 with carmustine wafer.
  • Any prior treatment with an intracerebral agent.
  • Receiving additional, concurrent, active therapy for GBM outside of the trial
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: Control Arm

Newly Diagnosed GBM: Radiation therapy (XRT) 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation, and the start of the first cycle of Maintenance Therapy 2-6 weeks after the last day of radiotherapy. The start of all subsequent maintenance therapy cycles (2-12) every 4 weeks + 7 days after the first daily dose of temozolomide of the preceding cycle. Total number of cycles should comply with institutional or country standards. During maintenance therapy, the first cycle of temozolomide will be at 150 mg/m2 for Days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for Days 1-5 of a 28-day cycle.

Recurrent GBM: Lomustine started at 110 mg/m2/day on Day 1 of a 42-day cycle as per local standards. Treatment will continue for up to 6 total cycles.
Arzneimittel: Temozolomide

Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg

Andere Namen:
  • Temodar
  • Temodal
  • Temcad
Arzneimittel: Lomustine

Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg

Andere Namen:
  • CCNU
  • CeeNU
  • Glöstin
Strahlung: Radiation

60 Gy
Experimental: Regorafenib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).

Recurrent GBM: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).
Arzneimittel: Regorafenib

Dosage Form: Tablet for oral administration Strength: 40 mg Standard Regimen: 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

Andere Namen:
  • BUCHT 73-4506
  • Stivarga
Experimental: Paxalisib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles.

Recurrent GBM: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 21 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 21 days for all subsequent cycles.
Arzneimittel: Paxalisib

Dosage Form: Tablet for oral administration Strength: 15 mg Standard Regimen: 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles

Andere Namen:
  • GDC-0084
Experimental: VAL-083 Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.

Recurrent GBM: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.
Arzneimittel: VAL-083

Dosage Form: Infusion for intravenous administration Strength: 40 mg per vial Standard Regimen: 30 mg/m2 on Day 1, 2 and 3 of 21-day cycle. The drug is available in powder form. It is reconstituted with 5 mL of 0.9% Sodium Chloride for Injection, USP. This will produce a solution of 40 mg VAL-083 in 5 mL. The required volume of reconstituted VAL-083 for the patient is then calculated at the rate of 30 mg/m2. The corresponding volume is further diluted into 250 mL of 0.9% Sodium Chloride for Injection, USP, prior to intravenous administration.

Andere Namen:
  • Dianhydrogalactitol
Experimental: VT1021 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. Treatment as outlined in section "Experimental: VT1021 Treatment Arm" with the first 6 patients receiving VT1021 at 12 mg/kg twice weekly in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities reported, the dose will be de-escalated to 9 mg/kg two times a week. 6 patients will then be receiving 9 mg/kg two times a week and observed for DLTs for 4 weeks.

Recurrent GBM: Dose Finding Phase is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Arzneimittel: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM)

Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM) Newly diagnosed MGMT Methylated and Unmethylated GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. PK and PD assessments are done for patients as a part of ESM. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.

Recurrent GBM: ESM is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Arzneimittel: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: VT1021 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: As confirmed through the dose finding phase) twice weekly during radiation therapy. Rest period: 2-6 weeks from last day of radiation. VT1021 dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with VT1021. After 6 cycles, VT1021 only.

Recurrent GBM: VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: 12mg/kg) twice weekly.
Arzneimittel: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: Troriluzole Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. The first 6 patients will receive troriluzole at 100 mg BID for the first two weeks followed by 200 mg BID for the next two weeks in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 100 mg in the morning and followed by 200 mg in the evening. 6 patients will receive this dose and observed for 4 weeks. If there are two DLTs reported, then this dose will be de-escalated to 100 mg BID. 6 patients will then be receiving this dose and observed for DLTs for 4 weeks.

Recurrent GBM: Rolling 6 design. The first 6 patients receiving troriluzole 100 mg twice a day (BID) for the first two weeks followed by 200 mg BID for the next two weeks in combination with lomustine. The dose de-escalation is similar to that of newly diagnosed patients during the rolling 6 design.
Arzneimittel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andere Namen:
  • BHV-4157
Experimental: Troriluzole Treatment Arm - Enhanced Safety Management (ESM)

Newly diagnosed MGMT Methylated and Unmethylated GBM and Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Arzneimittel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andere Namen:
  • BHV-4157
Experimental: Troriluzole Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. Rest period: 2-6 weeks from last day of radiation. Troriluzole dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with troriluzole. After 6 cycles, troriluzole only.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. After 6 cycles, troriluzole only.
Arzneimittel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andere Namen:
  • BHV-4157
Experimental: ADI-PEG 20 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Dose Finding Phase is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Rolling 6 design. The first 6 patients will receive ADI-PEG 20 at 36 mg/m2 once a week in combination with lomustine 100 mg/m2 orally on day 1 of a 42-day cycle. 6 patients will receive this dose and be observed for 4 weeks. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 18 mg/m2 once a week. 6 patients will receive this dose and be observed for 4 weeks.
Biologisch: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andere Namen:
  • Pegargiminase
Experimental: ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)

Newly diagnosed MGMT Methylated and Unmethylated GBM: ESM is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Biologisch: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andere Namen:
  • Pegargiminase
Experimental: ADI-PEG 20 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy over 6 weeks. Temozolomide (75 mg/m2 orally daily and ADI-PEG 20 (Dosage Form: Solution for intramuscular injection; Strength: 11.5 ± 1.0 mg/ml; Dose: 36 mg/m2) once a week. Rest period: 2-6 weeks from last day of radiation. ADI-PEG 20 dosing will continue during rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Subsequent cycles will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with ADI-PEG 20. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with ADI-PEG 20 (Dosage Form: Solution for IM injection; Strength: 11.5 ± 1.0 mg/ml; Dose: As confirmed by dose finding phase, once a week. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.
Biologisch: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andere Namen:
  • Pegargiminase
Experimental: AZD1390 Treatment Arm

Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks in combination with AZD1390 given on days of radiation followed by 14 days with daily AZD1390. Rest Period 2-4 weeks from the last day of AZD1390. The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle, if there is no toxicity. Temozolomide will be administered for up to 6 cycles in the maintenance phase.
Arzneimittel: AZD1390

Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
Experimental: Tinostamustine - Dose finding phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Tinostamustine Dosage Form: Infusion for intravenous administration; Rolling 6 design. Treatment as outlined in "Investigational: Tinostamustine Treatment Arm" with the first 6 patients receiving Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations. If there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).

Recurrent GBM: Rolling 6 design. Tinostamustine Dosage Form: Infusion for intravenous administration; Strength: Starting dose 80 mg/m2 on Day 1 of 21-day cycle for up to 12 cycles. The first 6 patients will receive Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations if there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).
Arzneimittel: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andere Namen:
  • EDO-S101
Experimental: Tinostamustine - Enhanced Safety Management

Newly diagnosed MGMT Methylated and Unmethylated GBM: Treatment as outlined in "Investigational: Tinostamustine Treatment Arm". Dose as determined by the dose finding phase.

Recurrent GBM: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase on Day 1 of 21-day cycle for up to 12 cycles.
Arzneimittel: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andere Namen:
  • EDO-S101
Experimental: Investigation arm: Tinostamustine

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT total of 60 Gy (2 Gy/fraction) over 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation. Tinostamustine treatment period: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase) on Day 1 of 21-day cycle for up to 12 cycles.
Arzneimittel: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andere Namen:
  • EDO-S101

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Overall Survival (OS)
Zeitfenster: From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Overall survival is defined from the time of randomization to death from any cause. Patients still alive at the time of an analysis will be considered censored at their date of last contact.
From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Progression-free survival (PFS)
Zeitfenster: From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Progression-free survival is defined as the time from randomization to clinically determined progression or death from any cause. All participants will be included in the analysis of PFS.
From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Tumor Response
Zeitfenster: From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Tumor response is categorized by Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Response captured from initiation of study treatment until disease progression.
From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Duration of Response (CR + PR)
Zeitfenster: From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Duration of response (CR+PR) is defined as time from date of response to date of clinically determined disease progression or death from any cause.
From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Global Coalition for Adaptive Research

Mitarbeiter

Bayer
AstraZeneca
Kazia Therapeutics Limited
Biohaven Pharmaceuticals, Inc.
Kintara Therapeutics, Inc.
Vigeo Therapeutics, Inc.
Polaris Group
Knoa Pharma

Ermittler

  • Hauptermittler: Tim Cloughesy, MD, GCAR CMO and GBM AGILE Global PI

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

30. Juli 2019

Primärer Abschluss (Geschätzt)

1. Juni 2028

Studienabschluss (Geschätzt)

1. Juni 2030

Studienanmeldedaten

Zuerst eingereicht

23. Mai 2019

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

30. Mai 2019

Zuerst gepostet (Tatsächlich)

31. Mai 2019

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

2. November 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

29. Oktober 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • GCAR-7213

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

UNENTSCHIEDEN

Beschreibung des IPD-Plans

Global Coalition for Adaptive Research (GCAR) is in the planning stages at this time.

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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